Photoacoustic (PA) imaging is a noninvasive imaging technique that may be used in medical environments, e.g., to detect, inter alia, vascular disease, skin abnormalities and some types of cancer. PA imaging generally involves flashing a laser at low energy with a near-infrared wavelength onto a target area or region. Infrared light penetrates relatively deeply into the body. This creates a large radiated area for a more detailed picture. Rapid absorption of laser energy expands the tissue (composed of microscopic absorbers) through transient thermo-elastic expansion. The pulsating expansion creates ultrasonic acoustic waves that can be detected by ultrasound detectors of appropriate sensitivity, e.g., ultrasound transducers. The transducer readings can be processed and interpreted using different mathematical equations/algorithms to create two- or three-dimensional images of the target area, showing the tissue structure via spatial distribution of microscopic absorbers or the flow of a bloodstream carrying the absorbers.
PA imaging is effective in anatomical applications based on its unique contrast mechanism. Typically, each tissue or target region absorbs different amounts of the laser energy, making each different target region or tissue potentially unique from a PA imaging standpoint. For purposes of blood vessel-related imaging, hemoglobin generally exhibits high optical contrast when a near-infrared wavelength is applied. This contributes to the sensitivity of blood vessel imaging with PA techniques, enabling doctors/health care providers to see abnormalities in the skin, vascular disease and cancer which can then be treated directly. PA images can be combined with those from other modalities (e.g., ultrasound) to create highly detailed depictions of the target area with complementing contrast. For example, the generated images may facilitate valuable diagnostics, e.g., allowing clinicians to identify small lesions that may be difficult to pick up using other techniques/technologies.
Recently, there have been developed PA contrast agents whose constituent particles are dimensioned down to the nanometer level and are considerably smaller than the microbubbles used in ultrasound imaging.
A PA contrast agent based on particles of nanometer proportion that can diffuse through blood vessels has been used to endocytose cells outside the vasculature. See U.S. Patent Publication No. 2008/0160090 to Oraevsky et al., entitled “Laser-Activated Nanothermolysis of Cells,” (hereinafter referred to as the “'090 publication”), the disclosure of which is incorporated by reference in its entirety.
However, this PA contrast agent and other PA contrast agents based on particles of nanometer dimension currently available and under development suffer from low sensitivity due to their low acoustical emission, owing to their small particle size.
Furthermore, incident optical pulsing is generally out of the reception bandwidth of ultrasound instrumentation and, thus, the optical energy is inefficiently converted into ultrasound signals.
Sufficiently energetic laser irradiation of “'090 publication” nanoparticles sufficiently large, or joined in big enough clusters, can produce surrounding microbubbles which would increase acoustical emission, but emergence of the microbubbles requires energizing to a level that thermomechanically destroys local tissue, in accordance with the tumor ablation function of that technique.
Microbubble-based ultrasound contrast agents offer certain recognized advantages in enhancing regular backscatter signals and generating distinct backscatter signals (e.g., super-harmonics and sub-harmonics of incident ultrasound waves) within the ultrasound receive passband. (See, e.g., Shi W T, Forsberg F, Liu J B, Merritt C R B, Goldberg B B: “New US media boosts imaging quality,” Diagnostic Imaging Global: Special Supplement, November 2000, pp 8-12.)
However, the relatively large size, i.e., of a microbubble, makes known microbubble-based contrast agents unavailable for measuring vascular parameters, such as permeability.
The use of nano-bubbles—which potentially would overcome the limitations associated with known microbubble-based agents—in ultrasound backscatter imaging has not been realized for several reasons. For example, the lifetime of a nano-bubble is too short for intravenous injection and subsequent human circulation, mainly because of the tremendous surface tension against the shell material in this size range. Additionally, the backscatter cross-section of such nano-bubbles is very small. Since backscatter cross-section is determined by the 6th power on scatterer size, a factor of 10 reduction in bubble diameter may lead to a 106 times (60 dB) reduction in backscatter power, which is a diminishing return.